Measurement of Porphyrins and Precursors

Fluorescence of urine under ultraviolet (UV) light is recommended as the initial screening test for the acute porphyrias,¹ whereas plasma fluorescent spectroscopy is the best initial test for diagnosis of cutaneous porphyrias.² Diverse techniques such as high-pressure liquid chromatography,³ quantitative extraction, and various forms of fluorometry are used to measure porphyrins and precursors.⁴ The International Federation of Clinical Chemistry and Laboratory Medicine presents diagnostic information on the Internet (www.ifcc.org).

Precipitating Factors in Acute Porphyria

Most patients who have inherited acute porphyria enjoy normal health and go through life without any knowledge of their disorder or ever experiencing an acute attack. All porphyric patients, however, are at risk for developing an attack if exposed to various precipitating factors. Drugs are the most common precipitating agents. Other factors that may trigger attacks include alcohol ingestion, reduced caloric intake (from fasting or dieting), and infection. Smoking can cause more frequent attacks.

Hormonal status is also important. Attacks are more common in females, and they rarely occur before puberty or after menopause. Pregnancy and oral contraceptives may also precipitate attacks. Some women experience regular attacks, commencing in the week before the onset of menstruation. These may require luteinizing hormone–releasing hormone (LH-RH) antagonists for control (Table 10-4).

Differential Diagnosis of Acute Intermittent Porphyria

Attacks of acute porphyria must be distinguished from other causes of acute abdominal pain or peripheral neuropathy sometimes associated with psychosis.⁷ Heavy metal poisoning (i.e., lead or arsenic) and Guillain-Barré syndrome must be considered, as well as paroxysmal nocturnal hemoglobinuria with its characteristic early morning hemoglobinuria and abdominal pain.⁷

During an attack, all patients excrete a massive excess of the porphyrin precursors, 5-aminolevulinic acid (ALA) and porphobilinogen (PBG), in their urine. Urine, when first voided, is clear and darkens on exposure to light as the hexa-hydroporphyrins, the porphyrinogens, are oxidized to porphyrins.

A rapid screening test during an acute attack is to mix equal volumes of urine and Ehrlich aldehyde reagent and observe for the pink color of porphobilinogen; alternatively the urine can be left standing in sunlight to observe darkening in color. The differential diagnosis of porphyrias uses qualitative and quantitative measurement of porphyrins and precursors, with subsequent use of enzymatic assay and identification of familial genetic alterations.⁸

Table 10-4 Precipitating Factors in Acute Porphyria